Overdose on acetaminophen (more commonly known by the brand name Tylenol(R)), accounts for 56,000 emergency room visits and more than 450 deaths annually in the USA. Acetaminophen overdose can occur by a single event of exceeding the recommended daily dosage. Overdose on acetaminophen is facilitated by the fact that it is a common ingredient in over-the-counter medications for cold, allergies, and congestion, conditions for which people often take multiple medications. The hepatotoxicity of acetaminophen is due to N-acetyl-p- benzoquinoneimine (NAPQI), which is generated by oxidative metabolism. Proposed herein are new 1,2-azaborines, wherein a CC bond pair of an arene is replaced with an isosteric boron- nitrogen unit that is designed to eliminate the formation of the toxic metabolite. This proposal seeks to: 1) synthesize novel 1,2-azaborine-based derivatives of acetaminophen, 2) determine their cytotoxicity and pharmacokinetics via appropriate in vitro tests, and 3) identify compounds to be studied in a Phase II STTR application. PUBLIC HEALTH RELEVANCE: Novel Azaborine Derivatives Predicted to Eliminate Acetaminophen Hepatotoxicity Overdose on acetaminophen (more commonly known by the brand name Tylenol(R)), accounts for 56,000 emergency room visits and more than 450 deaths annually in the USA. The toxicity of acetaminophen to the liver is due to a metabolic by-product. Proposed herein are new boron-nitrogen-containing analogues of acetaminophen that are designed to eliminate the formation of that metabolic by-product.